P357: MULTICENTER RETROSPECTIVE ANALYSIS OF CLINICAL OUTCOME OF ADULT PATIENS WITH MIXED-PHENOTYPE ACUTE LEUKEMIA (MPAL) DIAGNOSED AND TREATED IN THE LAST TEN YEARS. A CAMPUS-ALL STUDY.
Authors: D. Lazzarotto, I. Tanasi, A. Vitale, M. Piccini, M. Dargenio, F. Giglio, F. Forghieri, N. Fracchiolla, M. Cerrano, E. Todisco, C. Papayannidis, M. Leoncin, M. Defina, F. Guolo, C. Pasciolla, M. Delia, P. Chiusolo, A. Mulè, A. Candoni, M. Bonifacio, G. Pizzolo, R. Foà
Journal: HemaSphere (2022)

Background: Mixed phenotype acute leukemia (MPAL) is a very rare disease in adults. Most data derive from small retrospective series, some including also pediatric patients. Generally, treatment is similar to that of acute lymphoblastic leukemia (ALL), but the outcomes in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. Aims: Purpose of this retrospective study was to provide data on a large cohort of adult patients diagnosed and treated in 18 Italian hematology centers in the last 10 years. Methods: Seventy-seven adult patients diagnosed with MPAL according to the EGIL and WHO criteria in the last 10 years (2011-2021) and treated with curative intent were included in the study. Endpoints were the CR rate after induction, overall survival (OS), disease-free survival (DFS) and rate of AlloSCT. Results: Forty-eight of the 77 (62%) patients had B/myeloid MPAL, 27 (35%) had T/myeloid MPAL and 2 (3%) had B/T/myeloid MPAL. Median age at diagnosis was 49 years (range 17 - 77); it was lower in patients with T/myeloid MPAL than in B/myeloid MPAL cases (39 vs 54 years, P=0.04). Extramedullary involvement was detected in 26/77 (34%) of patients (mainly lymph nodes and spleen), but none had a central nervous system involvement. Cytogenetic analysis was normal in 40% of patients; 36% of cases had a complex karyotype, 24% had other cytogenetic abnormalities (including 8% with a BCR-ABL1 rearrangement). FLT-ITD mutation was detected in 14% of patients. No differences were found between B/myeloid and T/myeloid MPAL cases. Thirty/77 (39%) of patients were treated with an acute myeloid leukemia (AML)-like induction regimen, while 47 (61%) were treated with an ALL-like induction. Globally, CR rate after induction was 62% and 42% of these cases were also MRD negative. Patients treated with an AML-like induction had a higher rate of refractory disease after induction (33% vs 10%, P=0.02). The death during induction (DDI) rate was similar in the 2 groups (7% vs 8%). In univariate analysis an ALL-like therapy was the only variable associated with a better CR rate (P=0.0447). Patients refractory to AML-like induction were mainly salvaged with a subsequent AlloSCT or ALL-like therapy followed by an AlloSCT, and 60% of them achieved a CR. The median OS and DFS of the entire cohort were respectively 41.9 and 37.6 months, with an OS and DFS at 5 years of 43% and 39%, respectively. Age, type of induction therapy, karyotype, presence of FLT3-ITD mutation, extramedullary involvement and type of MPAL (B/myeloid vs T/myeloid) were tested in univariate analysis for OS and DFS. Age below 60 years was the only variable associated with a better OS (median OS of 67 months vs 26 months, P=0.0138), while no variable impacted on DFS. AlloSCT was performed in 50 patients (65%), 80% of them (40 patients) as part of the frontline treatment (36/40 patients transplanted in CR1). Among transplanted patients, we observed a 5-year OS of 54% (median not reached), that improved to 69% in patients transplanted as part of the frontline treatment. Summary/Conclusion: This study describes one of the largest cohorts of adult patients with MPAL. These data outline that this disease responds better to ALL-like induction therapy than to AML-like therapy and that consolidation therapy should include, whenever possible, an AlloSCT. Prospective studies are needed to uniform the therapeutic approach and to identify variables capable of predicting outcome and to guide therapy.